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Carbon ion radiotherapy (CIRT) shows substantial immunomodulatory potential due to distinct biological properties, including tumor-associated antigen exposure, enhanced immune-cell infiltration and activity, and immune microenvironment remodeling after CIRT. This review consolidates recent progress in combining heavy-ion radiotherapy with immunotherapy, covering preclinical and clinical evidence and highlighting future clinical foundations and theoretical 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Gaipl,  \nUniversity Hospital Erlangen, Germany  \nREVIEWED BY  \nAlexandros G. Georgakilas,  \nNational Technical University of Athens, Greece  \nMarco Durante,  \nHelmholtz Association of German Research Centres (HZ), Germany  \n*CORRESPONDENCE  \nJuntao Ran  \n [ranjt@lzu.edu.cn](ranjt@lzu.edu.cn)  \nRECEIVED 16 November 2025  \nREVISED 04 February 2026  \nACCEPTED 09 February 2026  \nPUBLISHED 25 February 2026  \nCITATION  \nChen R, Ma Q, Pan Y, Zhang T, Zhang Z, Di C and Ran J (2026) Combined carbon ion radiotherapy and immunotherapy: leveraging the immunological advantages of carbon ion.  \nFront. Immunol. 17:1747607 .  \ndoi: 10.3389/fimmu.2026.1747607  \nCOPYRIGHT  \n© 2026 Chen, Ma, Pan, Zhang, Zhang, Di and Ran. This is an open-access article distributed under the terms of the  \nCreative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nCombined carbon ion radiotherapy and immunotherapy: leveraging the immunological advantages of carbon ion  \nRuiming Chen 1, Qinqin Ma 1, Yuan Pan 1, Tanglong Zhang 1, Zhuoya Zhang 1, Cuixia Di 2 and Juntao Ran 3*  \n1The First Clinical Medical College of Lanzhou University, Lanzhou, China, 2 Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China, 3 Department of Radiation Oncology, the First Hospital of Lanzhou University, Lanzhou, China  \nImmunotherapy represents a systemic approach to cancer treatment; however, its effectiveness can be limited by intrinsic tumor resistance or immunosuppressive mechanisms within the tumor microenvironment. In contrast, carbon ion radiotherapy (CIRT) demonstrates considerable immunomodulatory potential owing to its distinct biological properties. The exposure of tumor-associated antigens, increased immune cell infiltration and activity, and modifications in the immune microenvironment after CIRT provide a mechanistic rationale for combining CIRT with immunotherapy. Furthermore, strategies aimed at converting the tumor microenvironment from immunosuppressive to immunostimulatory, or those targeting immune checkpoints, are currently under active exploration. This review summarizes the latest advances in combining heavy ion radiotherapy with immunotherapy, encompassing both preclinical and clinical studies. Based on the immunological advantages of CIRT, it provides a comprehensive summary and in-depth exploration of the potential of this combined treatment modality for future clinical applications, along with a theoretical foundation to support it.  \nKEYWORDS  \ncarbon ions radio therapy, combined therapy, heavy-ion, immunotherapy, radioimmunity  \n1 Introduction  \n1.1 Advantages of CIRT  \nHeavy-ion therapy (HIT) is currently one of the most advanced forms of radiotherapy. Heavy ions, defined as charged particles heavier than protons, encompass a range of species, including carbon, helium, neon, silicon, nitrogen, and argon, among which carbon ions are the most widely used in clinical practice (carbon ion radiotherapy, CIRT) (1). When heavy ions penetrate tissue, the velocity of the heavy ions decreases near the end of their range, leading to a sharp increase in the probability of ionization collisions and a concentrated release of energy, thereby producing the Bragg peak (2). This results in highly precise energy  \nFrontiers in Immunology 01 [frontiersin.org](frontiersin.org)  \ndeposition within the tumor region. Compared with conventional X −rays therapy (XRT), this characteristic not only significantly increases the energy delivered to the tumor, but also reduces radiation damage to the surrounding normal tissues. (Figure 1) .  \nHe","cbCaigBC84697d6r","https://ap.wps.com/l/cbCaigBC84697d6r","pdf",1306537,14,"English","# Introduction\n## Advantages of CIRT\n## Limitations of immunotherapy","[{\"question\":\"Why can immunotherapy be limited in cancer treatment?\",\"answer\":\"Immunotherapy effectiveness may be constrained by intrinsic tumor resistance and immunosuppressive mechanisms in the tumor microenvironment.\"},{\"question\":\"What immunological effects does carbon ion radiotherapy (CIRT) have after tumor exposure?\",\"answer\":\"CIRT can increase tumor-associated antigen exposure, strengthen immune-cell infiltration and activity, and modify the immune microenvironment toward an immunologically favorable state.\"},{\"question\":\"What is the mechanistic rationale for combining CIRT with immunotherapy?\",\"answer\":\"By converting the tumor microenvironment from immunosuppressive to immunostimulatory and by engaging immune-related targets such as immune checkpoints, CIRT can enhance anti-tumor immune responses that support immunotherapy.\"}]","Combined carbon ion radiotherapy and immunotherapy: leveraging the immunological advantages of carbon ion | PDF",1790117247,35]